Impact of Fasudil on cardiac and plasma Angiotensin(1-7) in pressure-overload rats

Objective Rho-kinase inhibition displays an activity against cardiac fibrosis,though its mechanism has not been fully elucidated. The present study was to investigate the impact of fasudil,a Rho kinase inhibitor,on cardiac and plasma AngiotensinⅡ( AngⅡ) and Angiotensin( 1-7) [Ang( 1-7) ]in pressure-overload rats. Methods Pressure-overload models were made in SD rats by abdominal aorta constriction,and 4 weeks after surgery the animals were randomly divided into 4 groups: sham,model,highdose fasudil( HF,30 mg per kg per d) and low-dose fasudil( LF,10 mg per kg per d). At 8 weeks after surgery,the left ventricle /weight index( LVWI) was calculated,the content of cardiac hydroxyproline( HYP) measured using alkaline hydrolysis,myocardial histopathology and interstitial fibrosis observed by HE and masson staining,and the concentrations of cardiac and plasma AngⅡ and Ang( 1-7) detected by ELISA. Results Compared with the sham group,the model group showed significantly elevated contents of LVWI and HYP( P 0. 01),much more collagen deposited in the myocardial interstitium,increased concentration of cardiac and plasma AngⅡ,and decreased level of cardiac Ang( 1-7)( P 0. 01),but a similar level of plasma Ang( 1-7). In comparison with the model group,the HF and LF groups exhibited reduced contents of LVMI and HYP and decreased deposition of interstitial collagen. The concentrations of cardiac and plasma AngⅡ were reduced to normal,while cardiac and plasma Ang( 1-7) increased significantly in the HF group( P 0. 01). The concentrations of cardiac and plasma AngⅡwere significantly reduced( P 0. 05),while Ang( 1-7) remarkably increased in the LF group( P 0. 01). Conclusion Fasudil can attenuates pressure-overload mediated cardiac fibrosis,which may be associated with the reduced level of AngⅡ and increased level of Ang( 1-7).